Q B Li1, L Chang2, F Ye3, Q H Luo2, Y X Tao4, H H Shu5. 1. Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China; Department of Anesthesiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Department of Anesthesiology, Tianjin Children's Hospital, Tianjin, China. 2. Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China. 3. Department of Anesthesiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. 4. Department of Anesthesiology, New Jersey Medical School, The State University of New Jersey, Newark, NJ, USA; Neuroscience Research Institute, Zhengzhou University Academy of Medical Science, Zhengzhou, Henan, China. 5. Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China. Electronic address: shuhaihua@hotmail.com.
Abstract
BACKGROUND: Accumulated evidence suggests that spinal cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) may be implicated in the development of opioid-induced hyperalgesia. METHODS: Rats received subcutaneous fentanyl injections at different doses (20-80 μg kg-1), four separate times at 15-min intervals. Some rats only received fentanyl (60 μg kg-1 × 4 doses) with or without surgical incision. Fentanyl-induced hyperalgesia was evaluated via a tail-pressure or paw-withdrawal test. The concentrations of spinal COX-2, EP-1 receptor (EP-1R) mRNA, and PGE2 were measured. The effects of the COX-2 inhibitor, parecoxib (intraperitoneal 10 mg kg-1), or the EP-1R antagonist, SC51089 (intraperitoneal 100 μg kg-1), on hyperalgesia and spinal PGE2 were examined. RESULTS: Acute repeated injections of fentanyl dose-dependently induced mechanical hyperalgesia, which reached a peak at the 1st day and persisted for 1-4 days postinjection. This hyperalgesia could be partly or totally prevented by the pretreatment of either parecoxib or SC51089. Consistently, the levels of spinal COX-2 mRNA and PGE2 were also dose-dependently increased, reaching a peak at the first day and persisting for 2 days postinjection. Pretreatment with parecoxib could block the increase in spinal PGE2 and had no effects on spinal COX-2 and EP-1R mRNA. Fentanyl injection enhanced incision-induced mechanical and thermal hyperalgesia. CONCLUSIONS: Acute repeated fentanyl administration dose-dependently produced mechanical hyperalgesia and augmented surgery induced postoperative hyperalgesia. This behavioural change was paralleled with an increase in spinal COX-2 mRNA and PGE2 after fentanyl administration. Inhibition of COX-2 or blockade of EP-1R can partly or totally prevent hyperalgesia.
BACKGROUND: Accumulated evidence suggests that spinal cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) may be implicated in the development of opioid-induced hyperalgesia. METHODS:Rats received subcutaneous fentanyl injections at different doses (20-80 μg kg-1), four separate times at 15-min intervals. Some rats only received fentanyl (60 μg kg-1 × 4 doses) with or without surgical incision. Fentanyl-induced hyperalgesia was evaluated via a tail-pressure or paw-withdrawal test. The concentrations of spinal COX-2, EP-1 receptor (EP-1R) mRNA, and PGE2 were measured. The effects of the COX-2 inhibitor, parecoxib (intraperitoneal 10 mg kg-1), or the EP-1R antagonist, SC51089 (intraperitoneal 100 μg kg-1), on hyperalgesia and spinal PGE2 were examined. RESULTS: Acute repeated injections of fentanyl dose-dependently induced mechanical hyperalgesia, which reached a peak at the 1st day and persisted for 1-4 days postinjection. This hyperalgesia could be partly or totally prevented by the pretreatment of either parecoxib or SC51089. Consistently, the levels of spinal COX-2 mRNA and PGE2 were also dose-dependently increased, reaching a peak at the first day and persisting for 2 days postinjection. Pretreatment with parecoxib could block the increase in spinal PGE2 and had no effects on spinal COX-2 and EP-1R mRNA. Fentanyl injection enhanced incision-induced mechanical and thermal hyperalgesia. CONCLUSIONS: Acute repeated fentanyl administration dose-dependently produced mechanical hyperalgesia and augmented surgery induced postoperative hyperalgesia. This behavioural change was paralleled with an increase in spinal COX-2 mRNA and PGE2 after fentanyl administration. Inhibition of COX-2 or blockade of EP-1R can partly or totally prevent hyperalgesia.
Authors: Harald Lenz; Johan Raeder; Tomas Draegni; Fridtjof Heyerdahl; Martin Schmelz; Audun Stubhaug Journal: Pain Date: 2011-03-10 Impact factor: 6.961
Authors: L van Gulik; S J G M Ahlers; E M W van de Garde; P Bruins; W J van Boven; D Tibboel; E P A van Dongen; C A J Knibbe Journal: Br J Anaesth Date: 2012-07-24 Impact factor: 9.166